Morphology-based optimization of cardiac resynchronization therapy

ABSTRACT

A method and apparatus for delivering cardiac resynchronization therapy (CRT) in which an evoked response electrogram is recorded during one or more cardiac cycles and used to aid in the selection of resynchronization pacing parameters and/or to monitor the effectiveness of resynchronization therapy. The morphology of an evoked response electrogram may be recorded and analyzed to determine if and when intrinsic activation of one ventricle is occurring in order to optimally adjust the programmed atrio-ventricular (AV) delay interval for ventricular resynchronization pacing of a patient with intact AV node conduction.

RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. Nos. 10/003,718, filed on Oct. 26, 2001 and 10/251,629, filed onSep. 19, 2002 the disclosures of which are hereby incorporated byreference in their entirety.

FIELD OF THE INVENTION

This patent application pertains to methods and apparatus for thetreatment of cardiac disease. In particular, it relates to methods andapparatus for improving cardiac function with resynchronization therapy.

BACKGROUND

Implantable devices that provide electrical stimulation to selectedchambers of the heart have been developed in order to treat a number ofcardiac disorders. A pacemaker, for example, is a device which paces theheart with timed pacing pulses, most commonly for the treatment ofbradycardia where the ventricular rate is too slow. Atrio-ventricularconduction defects (i.e., AV block) and sick sinus syndrome representthe most common causes of bradycardia for which permanent pacing may beindicated. If functioning properly, the pacemaker makes up for theheart's inability to pace itself at an appropriate rhythm in order tomeet metabolic demand by enforcing a minimum heart rate. Implantabledevices may also be used to treat cardiac rhythms that are too fast,with either anti-tachycardia pacing or the delivery of electrical shocksto terminate atrial or ventricular fibrillation.

Implantable devices have also been developed that affect the manner anddegree to which the heart chambers contract during a cardiac cycle inorder to promote the efficient pumping of blood. The heart pumps moreeffectively when the chambers contract in a coordinated manner, a resultnormally provided by the specialized conduction pathways in both theatria and the ventricles that enable the rapid conduction of excitation(i.e., depolarization) throughout the myocardium. These pathways conductexcitatory impulses from the sino-atrial node to the atrial myocardium,to the atrio-ventricular node, and thence to the ventricular myocardiumto result in a coordinated contraction of both atria and bothventricles. This both synchronizes the contractions of the muscle fibersof each chamber and synchronizes the contraction of each atrium orventricle with the contralateral atrium or ventricle. Without thesynchronization afforded by the normally functioning specializedconduction pathways, the heart's pumping efficiency is greatlydiminished. Patients who exhibit pathology of these conduction pathways,such as bundle branch blocks, can thus suffer compromised pumpingperformance.

Heart failure refers to a clinical syndrome in which an abnormality ofcardiac function causes a below normal stroke volume that can fall belowa level adequate to meet the metabolic demand of peripheral tissues. Itusually presents as congestive heart failure (CHF) due to theaccompanying venous and pulmonary congestion. Heart failure can be dueto a variety of etiologies with ischemic heart disease being the mostcommon. Some heart failure patients suffer from some degree of AV blockor are chronotropically deficient such that their cardiac output can beimproved with conventional bradycardia pacing. Such pacing, however, mayresult in some degree of uncoordination in atrial and/or ventricularcontractions because pacing excitation from a single pacing site isspread throughout the myocardium only via the much slower conductingmuscle fibers of either the atria or the ventricles, and not thespecialized conduction pathways. Most pacemaker patients can stillmaintain more than adequate cardiac output with artificial pacing, butthe diminishment in pumping efficiency may be significant in a heartfailure patient whose cardiac output is already compromised.Intraventricular and/or interventricular conduction defects are alsocommonly found in heart failure patients and can contribute to cardiacdysfunction by causing unsynchronized contractions during intrinsicbeats. Other conduction defects can occur in the atria.

In order to treat these problems, implantable cardiac devices have beendeveloped that provide appropriately timed electrical stimulation to oneor more heart chambers in an attempt to improve the coordination ofatrial and/or ventricular contractions, termed cardiac resynchronizationtherapy (CRT). Ventricular resynchronization is useful in treating heartfailure because, although not directly inotropic, resynchronizationresults in a more coordinated contraction of the ventricles withimproved pumping efficiency and increased cardiac output. Currently, amost common form of CRT applies stimulation pulses to both ventricles,either simultaneously or separated by a specified biventricular offsetinterval, and after a programmed atrio-ventricular (AV) delay intervalwith respect to the detection an intrinsic atrial contraction ordelivery of an atrial pace. Appropriate specification of theseparameters is necessary in order to achieve the desired optimumcoordination between the atria and the ventricles and within theventricles, and it is this problem with which the present invention isprimarily concerned.

SUMMARY

The present invention relates to methods and apparatus for deliveringcardiac resynchronization therapy (CRT) in which an evoked responseelectrogram is recorded during one or more cardiac cycles and used toaid in the selection of resynchronization pacing parameters and/or tomonitor the effectiveness of resynchronization therapy. Analysis of themorphology of evoked response electrograms may be used to maintainoptimum hemodynamics by comparing recorded evoked response electrogramswith a template waveform representative of the optimum situation andadjusting one or more pacing parameters accordingly. Examples of pacingparameters which may be adjusted in accordance with a morphology-basedalgorithm include the pacing pulse energy, the atrio-ventricular (AV)interval for atrial tracking and AV sequential pacing modes, thebiventricular offset interval for biventricular pacing modes, and theparticular pacing mode to be used for delivering cardiacresynchronization therapy.

In one particular embodiment, the morphology of an evoked responseelectrogram is recorded and analyzed to determine if and when intrinsicactivation of the right ventricle is occurring in order to optimallyadjust the programmed atrio-ventricular (AV) delay interval forbiventricular or left ventricle-only (LV-only) resynchronization pacingof a patient with intact AV node conduction. Analysis of the morphologyof recorded evoked response electrograms can also be used to optimallyadjust the AV delay of a conventional dual-chamber pacemaker in whichonly one ventricle is paced. In another embodiment, morphology analysisis used to aid in monitoring the patient's condition by loggingsignificant changes made to pacing parameters by morphology-basedalgorithms and/or by classifying evoked response electrograms intodifferent events based upon their morphology and maintaining counts ofeach type of event.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a system diagram of an exemplary CRT device.

FIG. 2 shows an example evoked response electrograms.

FIGS. 3 and 4 illustrate exemplary algorithms for optimizing theprogrammed AV delay interval.

DETAILED DESCRIPTION

Cardiac devices configured for delivering resynchronization or otherpacing therapy may be programmed with a number of different parametersettings that affect the patient's cardiac performance. In abiventricular pacing mode, for example, pacing pulses may be deliveredto the right and left ventricles during a cardiac cycle with a specifiedoffset interval between the pulses designed to produce a synchronizedcontraction within the left ventricle and between both ventricles.Because of different conduction conditions in the two ventricles, theoptimum offset interval for producing a synchronized, and hence moreefficient, left ventricular contraction in a given patient may vary.Another parameter that affects cardiac performance is theatrio-ventricular (AV) delay interval used in atrial tracking modes,which may be employed for resynchronization as well as conventionalbradycardia pacing. In an atrial tracking mode, the ventricles arestimulated following an atrial intrinsic contraction or atrial pace sothat diastolic filling is augmented prior to ventricular systole. Theoptimum values for these CRT parameters as well as others which affectCRT performance vary not only from patient to patient but may alsochange over time in an individual patient. For example, the optimumvalue for the atrio-ventricular interval varies with heart rate and frompatient to patient. It would be desirable for a cardiacresynchronization device to possess a means of monitoring CRTperformance so that CRT parameters can be adjusted accordingly, eithermanually via an external programmer or automatically in accordance withan algorithm programmed into the device. The present invention relatesto methods and apparatus for accomplishing this objective by analyzingthe morphology of evoked response electrograms which show the timecourse of cardiac depolarization during a paced cycle as sensed by anelectrode. Such electrograms are referred to herein as testelectrograms. The morphology of such an evoked response electrogram maybe analyzed by comparing it with a template representing the optimum ordesired situation, where the comparison is performed by, for example,cross-correlating the test electrogram with the template or comparingidentifiable features of the test electrogram and template waveforms.One or more pacing parameters may then be adjusted in a manner whichwould tend to make a subsequent test electrogram conform to thetemplate. Among the pacing parameters which may be adjusted in thismanner are the pacing pulse energy, the pacing mode, theatrio-ventricular delay interval, and the biventricular offset interval.

One aspect of CRT performance which can be ascertained by morphologyanalysis of an evoked response electrogram is whether or not the pace orpaces delivered during a cardiac cycle have succeeded in capturing theheart, where capturing refers to causing sufficient depolarization ofthe myocardium that a propagating wave of excitation and contractionresult. In order for a pacing pulse to capture the heart, it must havesufficient energy, and it is desirable to minimize pacing pulse energyas much as possible while still providing reliable pacing. The use ofmorphology analysis of evoked response electrograms for captureverification and automatic adjustment of pacing pulse energy (referredto as autocapture) is described in U.S. patent application Ser. No.10/251,629 where a test evoked electrogram recorded during a CRT pacingcycle is compared against templates representing biventricular (BiV)capture, right ventricle-only (RV-only) capture, and left ventricle-only(LV-only) capture.

Besides pacing pulse energy, another factor which affects whether and towhat extent a pacing pulse captures the heart is intrinsic cardiacactivity. If a pace is delivered to a cardiac chamber shortly afterintrinsic excitation of the chamber during the refractory period, nofurther excitation occurs from the pace. If a pace is delivered to acardiac chamber while the chamber is depolarizing from intrinsicexcitation, a fusion beat results. The morphologies of evoked responseelectrograms recorded during such fusion beats and refractory paces aredifferent from the morphologies of electrograms recorded during paceswhich result in true capture. This can present a problem to devicesemploying a template-based autocapture system because fusion beats andrefractory paces may be falsely interpreted as indicative ofinsufficient pacing pulse energy. (Threshold autocapture systems mayalso falsely interpret fusion beats.) It is therefore desirable for thetiming of pacing pulses to be adjusted in a manner which preventsinterference with paces by intrinsic activity. For example, theprogrammed AV delay interval may be selected as a fixed value that ismuch shorter than the patient's intrinsic AV interval. If the programmedAV delay interval is short enough so that excitation resulting from apace always reaches the ventricular sensing site where the evokedresponse electrogram is recorded before the intrinsic excitation hastime to propagate to that site from the AV node, such evoked responseelectrograms will not change as the intrinsic AV interval varies withheart rate. For example, in the case of biventricular pacing cycleswhere there is a loss of capture in the right ventricle, evoked responseelectrograms recorded from the right ventricle during such cycles areinvariant with respect to changes in the patient's intrinsic AV intervalas long as the programmed AV delay interval is shorter than thepatient's intrinsic AV interval by a margin at least greater than thetime it takes for excitation to propagate from the paced left ventricleto the right ventricle.

A disadvantage of a fixed programmed AV delay interval, however, is thatthe hemodynamically optimum value for this parameter varies with rate.The heart rate in a normal individual increases in response to increasedmetabolic demand or emotional excitement due to hormonal and neuralinfluences, the latter being increased sympathetic discharge relative toparasympathetic discharge. The neural and hormonal influencesresponsible for the increased heart rate also increase the force ofcardiac contractions and decrease the intrinsic AV interval since theventricles need to be filled more rapidly during a shorter diastole ifcardiac output is to be increased. For optimum hemodynamics, animplanted pacemaker delivering either bradycardia or CRT ventricularpacing should vary the pacing rate and programmed AV delay interval inaccordance with metabolic demand in a manner that mimics the normalphysiological situation. In a chronotropically competent patient, theventricular pacing rate can be varied in accordance with metabolicdemand through the use of an atrial tracking mode in which the patient'snatural atrial rhythm controls the ventricular pacing rate. In achronotropically incompetent patient, rate-adaptive pacing modes can beemployed in which the atrial and ventricular pacing rate is controlledby a measured parameter reflective of metabolic demand such as activitylevel or minute ventilation. In either case, an implanted device can beprogrammed to vary its programmed AV delay interval along with theventricular pacing rate in a manner which maintains optimum hemodynamicperformance. This means that the programmed AV delay interval shouldmatch the patient's intrinsic AV interval, where “match” in this casemay mean that the programmed AV delay interval is always slightlyshorter than the intrinsic AV interval so that intrinsic excitation fromthe AV node does not affect evoked response electrograms recorded duringventricular pacing in patients with an intact AV conduction pathway. Anempirically derived look-up table or other mapping function can beemployed by the implantable device to map particular ventricular pacingrates to programmed AV delay intervals that are matched to the optimum.

Determining how a patient's intrinsic AV interval varies with either thenatural atrial rhythm or with the output of a metabolic demand sensorsuch as an accelerometer or minute ventilation sensor, however, isproblematic. Moreover, in any particular patient, the manner in whichthe intrinsic AV interval varies may change over time. It wouldtherefore be useful for an implanted device to have the capability ofdetecting when the programmed AV delay interval does not match thepatient's intrinsic AV interval and automatically adjusting theprogrammed AV delay interval so that it does match. In one embodiment ofthe present invention, an implantable CRT device is programmed to adjustthe programmed AV delay from recorded evoked response electrograms. Suchmorphology-based adjustment of the programmed AV delay may beimplemented in biventricular as well as conventional dual-chamber pacingmodes. The AV delay adjustment algorithm involves comparison of anevoked response electrogram with a template representing capture of aventricle or ventricles by a pacing pulse or pulses delivered at an AVdelay interval assumed to be optimum. The AV delay is then adjusted in amanner which causes the evoked response electrogram to more nearlyresemble the template.

One application of the morphology-based algorithm described above is tooptimize the AV delay interval for delivering CRT which requires nearly100% pacing of the ventricles to be effective. A morphology-based AVdelay optimization algorithm can also work to vary the AV delay tomaintain the ventricular morphology with rate. For instance, a rateincrease in a heart failure patient causes the intrinsic AV delay toshorten. If the programmed AV delay was not short enough at the newrate, intrinsic conduction would take over in the RV, reducing thebenefit of CRT. By optimizing the AV delay, this situation can beprevented so that biventricular pacing is always maintained. AV delayoptimization may also be employed in a standard dual chamber pacemaker(i.e., a device which paces one atrium and one ventricle). For instance,in a chronotropically competent patient, where the intrinsic AV delay isjust shorter or the same as the programmed AV delay, the optimizationalgorithm could be utilized to recognize this case and potential fusionbeats. A dynamic AV delay interval (i.e., one that is made to vary withrate) could be extended (within a boundary) to promote intrinsicconduction and to conserve energy. In this manner, the dynamic AV delaycould be tailored to each patient, rather than having the dynamic AVdelay that comes programmed in the device be an average of the AV delayresponse with rate from a study population. Additionally, as it may bebeneficial to promote ventricular pacing in some patients; the AV delayoptimization algorithm can insure this occurs.

An example of a morphology-based method for adjusting the AV delayinterval in a biventricular pacing situation is as follows. In order tomore sensitively detect intrinsic activation of the right ventricle, atemplate electrogram is recorded during an LV-only pace with aprogrammed AV delay interval known to be matched to the patient'sintrinsic AV interval. Periodically and/or at times when the patient'sintrinsic AV interval is expected to have changed (e.g., when thepatient's intrinsic heart rate changes from that which was present whenthe template electrogram was recorded), the device records a testelectrogram during an LV-only pace and compares it with the templateelectrogram. In the case where the evoked response electrograms arerecorded by an electrode in the right ventricle (such as a shockelectrode also used for delivering defibrillation shocks), a peak in theevoked response electrogram of an LV-only pace represents activation ofthe right ventricle via either intrinsic conduction from the AV node orthe spread of excitation from the paced left ventricle. The comparisonthen involves determining when the peaks in the test and templateelectrograms occur relative to the pace. If the peak in the testelectrogram occurs earlier than the peak in the template, it impliesthat intrinsic activation of the right ventricle from the AV node isoccurring and that the programmed AV delay interval should be shortenedif it is to match the intrinsic AV interval. Conversely, if the peak inthe test electrogram occurs later than the peak in the template, itimplies that the right ventricle is activated by the spread ofdepolarization from the paced left ventricle before intrinsic excitationcan arrive from the AV node and that the programmed AV delay intervalshould be lengthened in order to match the intrinsic AV interval. (Itshould be appreciated that the technique could also be applied using anRV-only pace with left ventricular sensing.) In a further refinement,the device determines matched programmed AV delay intervals in thismanner for a plurality of different pacing rates (as dictated by thepatient's natural atrial rhythm in the case of atrial tracking pacingmodes or by sensed exertion levels in the case of rate-adaptive pacingmodes). The matched AV delay intervals may then be used to form alook-up table or other function for mapping particular pacing rates toparticular programmed AV delay intervals. When the ventricular pacingrate changes, the device may then automatically adjust the programmed AVdelay interval accordingly.

Monitoring the morphology of evoked response electrograms recognizingchanges to that morphology over time can also be useful in providingimproved CRT delivery by allowing the user to re-optimize pacingparameters or perform some other adjustment to therapy based on analysisof this information. Such monitoring may be implemented, for example,by: 1) logging significant changes made to pacing parameters bymorphology-based algorithms, 2) maintaining counts of BiV capture,RV-only capture on a BiV pace LV-only capture on a BiV pace, fusion, andno capture, and comparing these evoked response classification countsagainst a threshold for automatic triggering of a CRT Monitor or otheralarm, 3) triggering of user notification based on long-term changes incapture morphology, 4) triggering of electrogram storage, along withstorage of other concurrent data such as accelerometer activity, basedon changes in capture morphology which may provide information such asthat the current programmed CRT is not optimal at elevated rates, and 5)monitoring during automatic adjustment to the programmed leftventricular protection period (LVPP) to ensure that optimal CRT isdelivered while maintaining the safety provided by LVPP. The LVPP is aperiod during which pacing of the left ventricle is inhibited and isused in biventricular or left ventricle-only pacing modes which arebased upon right ventricular sensing. Morphology-based algorithms canalso be used to determine whether the LVPP is being invoked by trueintrinsic depolarization or by far-field sensing. (See U.S. patentapplication Ser. No. 09/748,754, herein incorporated by reference, for afuller description of the left ventricular protection period.)

A description of an exemplary cardiac rhythm management device suitablefor delivering CRT therapy and recording evoked response electrograms isset forth below. The techniques for optimizing and monitoring CRTperformance discussed above may be implemented by appropriateprogramming of the device's controller. Descriptions of specificembodiments employing those techniques are also given.

1. Exemplary Device Description

Cardiac rhythm management devices such as pacemakers and ICDs aretypically implanted subcutaneously on a patient's chest and have leadsthreaded intravenously into the heart to connect the device toelectrodes used for sensing and delivery of electrical stimulation suchas defibrillation shocks and pacing pulses. A programmable electroniccontroller causes the pacing pulses to be output in response to lapsedtime intervals and sensed electrical activity (i.e., intrinsic heartbeats not as a result of a pacing pulse). Pacemakers sense intrinsiccardiac electrical activity by means of internal electrodes disposednear the chamber to be sensed. A depolarization wave associated with anintrinsic contraction of the atria or ventricles that is detected by thepacemaker is referred to as an atrial sense or ventricular sense,respectively. In order to cause such a contraction in the absence of anintrinsic beat, a pacing pulse (either an atrial pace or a ventricularpace) with energy above the capture threshold must be delivered to thechamber.

A system diagram of an exemplary cardiac rhythm management device fordelivering cardiac resynchronization therapy is illustrated in FIG. 1.The controller of the device is made up of a microprocessor 10communicating with a memory 12, where the memory 12 may comprise a ROM(read-only memory) for program storage and a RAM (random-access memory)for data storage. The controller could be implemented by other types oflogic circuitry (e.g., discrete components or programmable logic arrays)using a state machine type of design, but a microprocessor-based systemis preferable. The controller is capable of operating the device in anumber of programmed modes where a programmed mode defines how pacingpulses are output in response to sensed events and expiration of timeintervals. A telemetry interface 80 is provided for communicating withan external programmer 300. The external programmer is a computerizeddevice with a controller 330 that can interrogate the device and receivestored data as well as adjust various operating parameters.

The device has an atrial sensing/pacing channel comprising ringelectrode 33 a, tip electrode 33 b, sense amplifier 31, pulse generator32, and an atrial channel interface 30 which communicatesbidirectionally with a port of microprocessor 10. The device also hastwo ventricular sensing/pacing channels that similarly include ringelectrodes 43 a and 53 a, tip electrodes 43 b and 53 b, sense amplifiers41 and 51, pulse generators 42 and 52, and ventricular channelinterfaces 40 and 50. For each channel, the electrodes are connected tothe pacemaker by a lead and used for both sensing and pacing. A MOSswitching network 70 controlled by the microprocessor is used to switchthe electrodes from the input of a sense amplifier to the output of apulse generator. The device also includes a shock pulse generator 90interfaced to the controller and a shock lead which incorporates a tipelectrode 93 b and a coil electrode 93 a. Coil electrodes can be used todeliver pacing pulses but are designed especially for deliveringcardioversion/defibrillation shocks. The shock lead would normally bedisposed in the right ventricle (RV) so that sensing or pacing of theventricles may be performed using tip electrode 93 b and/or coilelectrode 93 a. A ventricular cardioversion/defibrillation shock may bedelivered between coil 93 a and the can 60 when fibrillation or othertachyarrhythmia is detected. The device also has an evoked responsesensing channel that comprises an evoked response channel interface 20and a sense amplifier 21 that has its differential inputs connected to aselected electrode and to the device housing or can 60 through theswitching network 70. The evoked response sensing channel may be used toverify that a pacing pulse has achieved capture of the heart in aconventional manner or, as explained below, used to record an evokedresponse electrogram.

The channel interfaces include analog-to-digital converters fordigitizing sensing signal inputs from the sensing amplifiers, registersthat can be written to for adjusting the gain and threshold values ofthe sensing amplifiers, and, in the case of the ventricular and atrialchannel interfaces, registers for controlling the output of pacingpulses and/or adjusting the pacing pulse energy by changing the pulseamplitude or pulse width. The microprocessor 10 controls the overalloperation of the device in accordance with programmed instructionsstored in memory. The sensing circuitry of the device generates atrialand ventricular sense signals when voltages sensed by the electrodesexceed a specified threshold. The controller then interprets sensesignals from the sensing channels and controls the delivery of paces inaccordance with a programmed pacing mode. The sense signals from any ofthe sensing channels of the pacemaker in FIG. 1 can be digitized andrecorded by the controller to constitute an electrogram that can eitherbe analyzed by the device itself or transmitted via the telemetry link80 to the external programmer 300.

As described above, CRT involves applying stimulus pulses to one or moreheart chambers in a manner that restores or maintains synchronizedcontractions of the atria and/or ventricles and thereby improves pumpingefficiency. Certain patients with conduction abnormalities mayexperience improved cardiac resynchronization with conventionalsingle-chamber or dual-chamber bradycardia pacing. For example, apatient with left bundle branch block may have a more coordinatedcontraction of the ventricles with a stimulus pulse than as a result ofan intrinsic contraction. More commonly, however, resynchronizationtherapy involves stimulating both ventricles in order to achieve betterintra-ventricular and inter-ventricular synchronous contraction. Betterintra-ventricular and inter-ventricular synchronization may beaccomplished in a biventricular resynchronization mode by stimulatingone ventricle at a specified biventricular offset interval with respectto a stimulus or sense occurring in the contralateral ventricle, thelatter being stimulated with a atrial tracking mode or not stimulated atall. For example, if the patient has left bundle branch block (LBBB), inwhich the left ventricle is activated much later than the rightventricle during an intrinsic beat, synchronization can be restored bypacing the right and left ventricles either simultaneously or at aspecified offset interval.

CRT may be most conveniently delivered in conjunction with a bradycardiapacing mode. Bradycardia pacing modes refer to algorithms used tostimulate the atria and/or ventricles when the intrinsic atrial and/orventricular rate is inadequate due to, for example, AV conduction blocksor sinus node dysfunction. Such modes may involve either single-chamberstimulation, where either an atrium or a ventricle is stimulated, ordual-chamber stimulation in which both an atrium and a ventricle arestimulated. A bradycardia pacing mode can enforce a minimum heart rateeither asynchronously or synchronously. In an asynchronous pacing mode,the heart is stimulated at a fixed rate irrespective of intrinsiccardiac activity. There is thus a risk with asynchronous stimulationthat a stimulus pulse will be delivered coincident with an intrinsicbeat and during the heart's vulnerable period which may causefibrillation. Most pacemakers for treating bradycardia today aretherefore programmed to operate synchronously in a so-called demand modewhere sensed cardiac events occurring within a defined interval eithertrigger or inhibit a stimulus pulse. Inhibited demand stimulation modesutilize escape intervals to control stimulation in accordance withsensed intrinsic activity. In an inhibited demand mode, a stimulus pulseis delivered to a heart chamber during a cardiac cycle only afterexpiration of a defined escape interval during which no intrinsic beatby the chamber is detected. If an intrinsic beat occurs during thisinterval, the heart is thus allowed to “escape” from stimulation by thedevice. Such an escape interval can be defined for each stimulatedchamber. For example, a ventricular escape interval can be definedbetween ventricular events so as to be restarted with each ventricularsense or stimulation. The inverse of this escape interval is the minimumrate at which the device will allow the ventricles to beat, sometimesreferred to as the lower rate limit (LRL).

In atrial tracking modes, another ventricular escape interval is definedbetween atrial and ventricular events, referred to as the programmed AVdelay interval. The programmed AV delay interval is triggered by anatrial sense or stimulus and stopped by a ventricular sense or stimulus.A ventricular stimulus pulse is delivered upon expiration of the AVdelay interval if no ventricular sense occurs before. Atrial-trackingstimulation of the ventricles attempts to maintain the atrio-ventricularsynchrony that occurs with physiological beats whereby atrialcontractions augment diastolic filling of the ventricles. As notedabove, the value of the programmed AV delay interval for optimalpreloading of the ventricles will vary from patient to patient and alsovaries with heart rate.

The electrical response of the heart to a pacing pulse is referred to asan evoked response. If the evoked response indicates that a propagatingwave of depolarization has resulted from the pacing pulse, it evidencesthat the paced chamber has responded appropriately and contracted. Anevoked response can therefore be used to verify that the pace hasachieved capture of the heart. An electrogram can also be recorded of anevoked response to a pace and used to determine if capture is achievedby comparing the recorded electrogram with a template electrogramrepresenting capture of the heart by a similarly delivered pace. Anevoked response sensing channel for recording an electrogram can be asensing channel normally used for other purposes or can be a sensingchannel dedicated to sensing evoked responses. In the embodimentillustrated in FIG. 1, a dedicated evoked response sensing channel isprovided where the differential inputs of sensing amplifier 21 may beconnected to a selected electrode and the can 60 by means of switchmatrix 70. An electrogram signal for morphology analysis is preferablyobtained from a unipolar electrode with a large surface area rather thana conventional bipolar sensing/pacing electrode. A large unipolarelectrode “sees” a larger volume of the myocardium, and changes in thedepolarization pattern of the ventricles will be more readily reflectedin an electrogram generated by the electrode during a ventricular beat.A convenient electrode for this purpose is the coil electrode that thedevice normally uses for delivering cardioversion/defibrillation shocks.The sensing channel incorporating the shock electrode and which is usedto generate electrograms for morphology analysis is referred to hereinas the shock channel.

2. Morphology-based Pacing Parameter Adjustment to Maintain OptimumHemodynamics

There are a number of methods which can be used to determine pacingparameters for bradycardia pacing or CRT which yield optimalhemodynamics including echocardiograms, pulmonary capillary wedgepressure (PCWP) measurements, and correlation of parameters with pulsepressure optimization. A general limitation of each of these methods isthat they are performed while the patient is at rest and in a sitting orprone position. The pacing settings that provide the physiologicallyoptimal hemodynamics at rest may not provide the same optimalhemodynamics when the patient is active or even standing. Factors suchas change in autonomic tone can come into play. Also, optimal pacingsettings may change over time, and the aforementioned methods aredifficult to implement as automatic algorithms executable by animplanted device. The present invention makes use of the fact that theelectrical morphology of the paced evoked response correlates to optimalhemodynamics. That is, for a given patient there is a correlationbetween the electrical morphology of the evoked response electrogram andwhether or not physiologically optimal hemodynamics are being achieved.An algorithm executable by the implanted device can thus maintainoptimal hemodynamics over a range of activity and heart rate bymodifying pacing parameters so that the morphology of evoked responseelectrograms is the same or similar to the morphology of a template,where the template may be an evoked response electrogram obtained whenoptimal hemodynamics are known to be present as determined by othermeans such as the methods noted above. In an exemplary method forsetting the pacing parameters of a cardiac rhythm management deviceimplanted in a patient, a pacing parameter is set to a plurality ofdifferent values while assessing the patient's hemodynamic performancein order to determine an optimum value which results in the besthemodynamic performance. The pacing parameter is then set to the optimumvalue, an evoked response electrogram is recorded during delivery of apace, and the recorded electrogram is stored as a template.Subsequently, during normal operation of the device, test evokedresponse electrograms are recorded during one or more cardiac cycles,and their morphologies are compared. The value of the pacing parameteris then automatically adjusted by the device so that the morphology of asubsequently recorded test electrogram will more nearly resemble themorphology of the template.

In one example implementation, a clinician first determines the pacingparameters that provide the most physiologically optimal hemodynamicsfor a specific patient. This determination may be based on input fromcommonly accepted practices for assessing hemodynamics. The clinicianthus manually reprograms the pacing parameters to obtain results fromechocardiograms or PCWP for a range of programming options. Once theclinician determines the optimal configuration, the clinician instructsthe device to store the paced evoked response electrogram as a template.

Alternatively, an external programmer may execute an algorithm forautomatic setting of pacing parameters, with the evoked responseresulting from the optimized pacing parameters automatically stored asthe template by the device. For example, the external programmer mayautomatically control the reprogramming of AV delay, biventricularoffset, or whatever pacing parameter is being optimized. The programmercould pace at each setting for a predetermined number of cardiac cycles(e.g., 10) or for a predetermined time (e.g., 10 ms), or it could holdat the current pacing parameter settings until the clinician instructsthe programmer to go to the next step. After the number of pacingparameters settings are exhausted, the implantable device is programmedto the settings determined as optimal. In one embodiment, theimplantable device stores the evoked response morphology at eachsetting, and these morphologies are displayed to the clinician so thatthe clinician can select which one, in his or her estimation, representsthe optimal morphology. The device then automatically programs thepacing parameters associated with that morphology and uses thatmorphology as its definition of “optimal” (i.e., as a template). Anotheroption is for the clinician to instruct the programmer that the currentpacing parameters under test are the optimal ones. The programmer thenautomatically reprograms the implantable device to those values with theevoked response morphology representing the “optimal” morphology storedas a template.

In another embodiment, the implantable device automatically determinesfrom all of the stored evoked response morphologies which evokedresponse morphology is the optimal. The device then automatically setsits pacing parameters to the parameter values associated with thatmorphology and uses that morphology as its definition of “optimal”(i.e., as a template). The steps to determine the optimal pacingparameters could be done on an automatic basis such as daily, monthly,or triggered by sensed conditions. The automatic determination of whichevoked response morphology is optimal could be based on criteria such asarea under the evoked response morphology curve, width of evokedresponse, time to peak of evoked response after pace. Automatic updatesmay be of a benefit since optimal pacing parameters may change due toremodeling of the heart, change in physical condition, change in drugregimen, and other factors.

3. Example Algorithm for Optimal Adjustment of Programmed AV DelayInterval

The programmed AV delay interval setting can cause significantmorphology changes and possibly create errors in a template-basedcapture determination algorithm. This effect is most significant whensensing an LV-only morphology from the right ventricle. FIG. 2 shows aBiV evoked response 201 and an LV-only evoked response 202 withdifferent AV delay intervals as recorded from the right ventricularshock channel. First, consider the case with a loss of RV capture(LV-only pacing) where the programmed AV delay interval is much shorterthan the intrinsic AV interval. Ventricular paces then occur in bothventricular chambers, but the device only captures the left side of theheart. The depolarization wavefront then propagates from the leftventricle to the right ventricle, causing a peak in the evoked responseelectrogram when the depolarization wavefront reaches the cardiac tissuenear the shock sensing coils. This tissue also enters a refractory stateallowing no further ventricular activity from any intrinsic signalspropagating through the AV node. This results in an LV-only evokedresponse much different from a BiV response, as shown by comparingwaveforms 201 and 202 in FIG. 2. Alternatively, consider a similar lossof RV capture, but with the AV delay interval programmed very near theintrinsic AV interval. A BiV pace again only captures the left side ofthe heart, but because of the small difference between the intrinsic andprogrammed AV delays, the intrinsic signal propagating through the AVnode depolarizes the right ventricle tissues before the wavefrontarrives from the left side. This results in a much earlier peak in theLV-only evoked response 203, more closely resembling the BiV response201. In this case, the device is essentially operating in aBiV-triggered mode.

These scenarios illustrate the errors that can be induced in templatematching if the programmed AV delay interval does not match theintrinsic delay. This becomes especially important in an ambulatorysetting where the patient's pacing rate and intrinsic AV delay maychange. Programming the AV delay much shorter than the intrinsic valueduring a threshold test provides one solution. In that case, the evokedresponse morphology is invariant if the difference between the intrinsicAV interval AV_(i) and the programmed AV delay interval AVD_(p) isgreater than the time it takes the depolarization wavefront to propagatefrom the left to right ventricle t_(LV→RV:)AV _(i) −AVD _(p) >t _(LV→RV)A dynamic AV delay is preferable for optimum hemodynamics, but only ifthe dynamic changes closely match the patient's intrinsic AV delayvariations will invariance in evoked response morphology be maintained.This presents an opportunity to optimize the dynamic AV delay for eachparticular patient; the degree of similarity of LV-only responses sensedfrom the right ventricle at different rates indicates the accuracy ofthe dynamic AV delay.

FIG. 3 shows a functional flowchart of an algorithm to optimize thedynamic AV delay setting at various rates to maintain ventricularresynchronization or provide an invariant morphology for an autocapturesystem which may be implemented in the programming of the devicecontroller. The algorithm is illustrated as steps 301 through 309 in thefigure. In this example, the pacing mode is changed from BiV to LV modeto analyze the morphology of the evoked response. As explained in theabove section, the intrinsic activity of a left bundle branch patientcontributes to a large variation of a LV pace when sensed from the rightventricle. It should be noted that a similar analysis could be performedin BiV mode, but the dynamic range and performance of the analysis willbe much less than from LV-only pacing. The LV-only template is capturedinitially at a base rate, for example 60 bpm. As the rate increases,templates are captured at the modified rate and compared with theinitial template. If they highly correlate, then the ventricularresynchronization has been maintained at the higher rate. If thetemplates at different rates do not correlate, then the algorithmexamines the relative time of the peaks of the two templates. A peak ofthe high-rate template occurring before the peak of the low-ratetemplate indicates intrinsic activity occurring in the right ventricle.In this case, the programmed AV delay is too long for the particularate, so the AV delay value at this particular rate is shortened.Alternatively, a peak of the high-rate template occurring after the peakof the low-rate template indicates a short AV delay value for theparticular rate. In this case, the programmed AV delay is lengthened atthis rate to maintain ventricular synchronization.

The algorithm described above can be incorporated into the functionalityof a heart failure device to supplement the pre-programmed dynamic AVdelay algorithm. FIG. 4 shows an example of one such implementation assteps 401 through 408. The clinician first sets the optimum ventricularresynchronization parameters, including the AV delay interval andbiventricular offset. The system then switches to LV-only pacing mode togather an LV-only template at the base rate from the RV shock channelelectrogram. The device then returns to normal heart failure therapyuntil a significant change in rate. Once a suitable rate change hasoccurred, the pacing output again switches to LV-only pacing for a fewbeats to gather a template at the higher rate. If there is no change inthe morphology, the system defaults to the preprogrammed dynamic AVdelay algorithm. If a morphology variation is noted, the system thenfinds the programmed AV delay value to return the ventricularresynchronization to the optimum settings. The new AV delay value couldbe stored in an AV delay vs. rate look-up table within the device.Alternatively, once several AV delay values have been found at differentrates, a curve could be fitted to these points to develop a newfunctional expression for AV delay vs. rate (e.g., a linear function).Note that a patient with no RV intrinsic activity would show novariations because of AV delay and would default to the preprogrammeddynamic AV delay function. Once the device determines the optimum AVdelay with rate, these values would supplement the preprogrammed dynamicAV delay function. This routine could be repeated at periodic intervalsfor example once per day, to check for variations from heart remodeling.

4. Example of Morphology-based Adjustment of Pacing Mode

If a biventricular pace is delivered near the intrinsic AV delay, one ofthe pace pulses may be into tissue which is refractory due to intrinsicactivation and, thus, may not be providing any additionalresynchronization therapy. Determining if this is occurring bymonitoring the evoked response morphology resulting from the programmedpacing provides an opportunity for CRT pacing energy management. Forexample, after determining whether a BiV pace is providing the samebenefit as an RV- or LV-only pace, the implantable device can eitherrecommend to the user to modify pace delivery or the system canautomatically change the pace delivery. This determination is done usingthe programmed parameters that are actual ambulatory settings. Thedevice may also determine whether a BiV pace is providing the samebenefit as an RV- or LV-only pace in certain rate ranges (e.g., in ratedependent LBBB). The device can then adjust pace delivery for differentzones such as delivering RV-only pacing in one zone (e.g., LRL to x) andBiV pacing in another zone (e.g., x to MPR). This determination couldoccur during a learning period or a defined treadmill test.

5. Morphology-based Wellness Monitoring

Monitoring the morphology of evoked response electrograms resulting fromCRT and recognizing changes to that morphology over time can be usefulin providing improved CRT delivery. Such monitoring allows the user tore-optimize pacing parameters or perform some other adjustment totherapy based on analysis of this information. In the case ofbiventricular pacing, a delivered BiV pace can have various end resultswhich effect the morphology of evoked response electrograms: the BiVpace may capture both ventricles, may capture only the right ventricle,may captures only the left ventricle, or may capture neither ventricle.In addition, measurable differences may occur in evoked responseelectrograms as the paced AV delay interval nears the intrinsic AVinterval. As discussed previously, optimal CRT may require a programmedAV delay interval near the intrinsic AV interval, and there is a need tomaintain an optimal AV delay over a wide range of heart rates. Themorphology of evoked response electrograms may change either abruptly orgradually over time affecting the end result of a BiV pace using currentprogrammed parameters and compromising optimal CRT. A gradual change inevoked response morphology may be the result of changes in the intrinsicAV interval due to, for example, cardiac remodeling, change in fitness,or change in drug regimen. An abrupt change in evoked responsemorphology may be the result of a change in drug regimen, silent heartattack, or other incident.

In one implementation of a method for tracking changes in evokedresponse morphology, the device is programmed such that counts aremaintained of BiV capture, RV-only capture on a BiV pace, LV-onlycapture on a BiV pace, intrinsic excitation of the right or leftventricle where the pace is delivered during the refractory period,fusion events where capture and intrinsic activity occur together, andno capture or excitation of either ventricle. The counts of each eventmay be further sorted into bins according to the pacing rate which wasin operation when the event occurred so that the frequency of occurrencefor each type of event can be correlated with pacing rate. Binningagainst pacing rate in this manner gives a clinician further insightinto impact of rate on current CRT programmed parameters. The counts ofeach type of event may also be compared against a threshold in order totrigger automatic data recording, user notification, or other alarm.Such triggering may occur, for example, when a specified percentage ofevents are not BiV captures, when a specified percentage of events areBiV fusion events, when a specified absolute number of events are notBiV captures, or when a specified absolute number of events are fusionevents. The user may want to re-optimize pacing parameters or performsome other adjustment to therapy based on an analysis of this systemfeedback. The information obtained in this manner thus improves aphysician's ability to evaluate the long-term effectiveness of currentCRT programmed parameters and alerts a physician to the possible loss ofCRT. The device may also be programmed to make operating adjustmentsautomatically in response to the gathered information.

Although the invention has been described in conjunction with theforegoing specific embodiments, many alternatives, variations, andmodifications will be apparent to those of ordinary skill in the art.Such alternatives, variations, and modifications are intended to fallwithin the scope of the following appended claims.

1. A method for operating a cardiac rhythm management device in apatient, comprising: delivering paces to both right and left ventriclesin accordance with a programmed biventricular pacing mode, such that thepaces are delivered at a programmed biventricular offset interval andafter a programmed AV delay interval with respect to an atrial event;switching to LV-only pacing mode and recording an evoked response testelectrogram during an LV-only pace with the programmed AV delayinterval; comparing the test electrogram to an evoked response templateelectrogram previously recorded during LV-only pacing when theprogrammed AV delay interval was known to be matched to the patient'sthen existing intrinsic AV interval; adjusting the programmed AV delayinterval to match the patient's current intrinsic AV interval based uponthe comparison of the test and template electrograms; returning to thebiventricular pacing mode with the adjusted AV delay interval.
 2. Themethod of claim 1 wherein the test electrogram is recorded from a rightventricular sensing channel.
 3. The method of claim 2 wherein thecomparing of the test and template electrograms further comprises:determining when peaks in the test and template electrograms occurrelative to the pace; shortening the programmed AV delay interval if thepeak in the test electrogram occurs earlier than the peak in thetemplate; and, lengthening the programmed AV delay interval if the peakin the test electrogram occurs later than the peak in the template. 4.The method of claim 1 further comprising determining matched programmedAV delay intervals at a plurality of different pacing rates.
 5. Themethod of claim 4 further comprising: using the matched AV delayintervals as determined at the plurality of pacing rates may to form amapping function which maps particular pacing rates to particularprogrammed AV delay intervals; and, automatically adjusting theprogrammed AV delay interval according to the mapping function as thepacing rate changes.
 6. The method of claim 5 wherein the mappingfunction is a look-up table.
 7. The method of claim 5 wherein themapping function is a linear function.
 8. A method for operating acardiac rhythm management device in a patient, comprising: deliveringpaces to both right and left ventricles in accordance with a programmedbiventricular pacing mode, such that the paces are delivered at aprogrammed biventricular offset interval and after a programmed AV delayinterval with respect to an atrial event; upon a change by a specifiedamount in a current pacing rate at which the right and left ventricularpaces are delivered, adjusting the programmed AV delay intervalaccording to a mapping function which maps a particular pacing rate to aparticular AV delay interval; switching to LV-only pacing mode andrecording an evoked response test electrogram during an LV-only pacewith the programmed AV delay interval; comparing the test electrogram toan evoked response template electrogram previously recorded duringLV-only pacing when the programmed AV delay interval was known to bematched to the patient's then existing intrinsic AV interval; if thetest and template electrograms do not sufficiently correlate, adjustingthe mapping function so that the programmed AV delay interval which ismapped to by the current pacing rate matches the patient's currentintrinsic AV interval based upon the comparison of the test and templateelectrograms; and returning to the biventricular pacing mode with theadjusted mapping function.
 9. The method of claim 8 wherein the testelectrogram is recorded from a right ventricular sensing channel and thecomparing of the test and template electrograms further comprises:determining when peaks in the test and template electrograms occurrelative to the pace; shortening the mapped to AV delay interval if thepeak in the test electrogram occurs earlier than the peak in thetemplate; and, lengthening the mapped to AV delay interval if the peakin the test electrogram occurs later than the peak in the template. 10.The method of claim 8 further comprising recording the test electrogramand comparing the test electrogram with the template electrogram only atperiodic intervals.
 11. A cardiac rhythm management device, comprising:pacing channels through which paces may be delivered to both right andleft ventricles; a controller programmed to deliver the paces inaccordance with a programmed biventricular pacing mode at a programmedbiventricular offset interval and after a programmed AV delay intervalwith respect to an atrial event; wherein the controller is programmedto: switch to an LV-only pacing mode and record an evoked response testelectrogram during an LV-only pace; compare the test electrogram to anevoked response template electrogram previously recorded during LV-onlypacing when the programmed AV delay interval was known to be matched tothe patient's then existing intrinsic AV interval; adjust the programmedAV delay interval to match the patient's current intrinsic AV intervalbased upon the comparison of the test and template electrograms; and,return to the biventricular pacing mode with the adjusted AV delayinterval.
 12. The device of claim 11 wherein the test electrogram isrecorded from a right ventricular sensing channel.
 13. The device ofclaim 12 wherein the controller is programmed to compare the test andtemplate electrograms by: determining when peaks in the test andtemplate electrograms occur relative to the pace; shortening theprogrammed AV delay interval if the peak in the test electrogram occursearlier than the peak in the template; and, lengthening the programmedAV delay interval if the peak in the test electrogram occurs later thanthe peak in the template.
 14. The device of claim 11 wherein thecontroller is programmed to determine matched programmed AV delayintervals at a plurality of different pacing rates.
 15. The device ofclaim 14 wherein the controller is programmed to: use the matched AVdelay intervals as determined at the plurality of pacing rates may toform a mapping function which maps particular pacing rates to particularprogrammed AV delay intervals; and, automatically adjust the programmedAV delay interval according to the mapping function as the pacing ratechanges.
 16. The device of claim 15 wherein the mapping function is alook-up table.
 17. The device of claim 15 wherein the mapping functionis a linear function.
 18. A cardiac rhythm management device,comprising: pacing channels through which paces may be delivered to bothright and left ventricles; a controller programmed to deliver the pacesin accordance with a programmed biventricular pacing mode at aprogrammed biventricular offset interval and after a programmed AV delayinterval with respect to an atrial event; wherein the controller isprogrammed to: upon a change by a specified amount in a current pacingrate at which the right and left ventricular paces are delivered, adjustthe AV delay interval according to a mapping function which maps aparticular pacing rate to a particular AV delay interval; switch toLV-only pacing mode and recording an evoked response test electrogramduring an LV-only pace; compare the test electrogram to an evokedresponse template electrogram previously recorded during LV-only pacingwhen the programmed AV delay interval was known to be matched to thepatient's then existing intrinsic AV interval; if the test and templateelectrograms do not sufficiently correlate, adjust the mapping functionso that the programmed AV delay interval which is mapped to by thecurrent pacing rate matches the patient's current intrinsic AV intervalbased upon the comparison of the test and template electrograms; andreturn to the biventricular pacing mode with the adjusted mappingfunction.
 19. The device of claim 18 wherein the test electrogram isrecorded from a right ventricular sensing channel and the controller isprogrammed to compare the test and template electrograms and adjust themapping function by: determining when peaks in the test and templateelectrograms occur relative to the pace; shortening the mapped to AVdelay interval if the peak in the test electrogram occurs earlier thanthe peak in the template; and, lengthening the mapped to AV delayinterval if the peak in the test electrogram occurs later than the peakin the template.
 20. The device of claim 18 wherein the controller isprogrammed to record the test electrogram and comparing the testelectrogram with the template electrogram only at periodic intervals.